The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy.

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00405015
First received: November 28, 2006
Last updated: August 23, 2010
Last verified: October 2008

November 28, 2006
August 23, 2010
April 2007
July 2008   (final data collection date for primary outcome measure)
Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.
Same as current
Complete list of historical versions of study NCT00405015 on ClinicalTrials.gov Archive Site
  • The effect of rosiglitazone as compared to placebo on the HOMA-index.
  • Changes in vital signs, body weight, clinical laboratory parameters and adverse events monitoring during the study.
Same as current
Not Provided
Not Provided
 
The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy.
The Effect of Rosiglitazone on Ischemia-reperfusion-injury Using Annexin A5 Scintigraphy. A Double Blind Placebo- Controlled Cross-over Study in Subjects With the Metabolic Syndrome

Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. In the present study, we will use annexinA5 scintigraphy to address the following hypothesis:

Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance.

Rationale: Cardiovascular disease is the leading cause of death in diabetic patients due to both a high event rate and a worse outcome. A pharmacological intervention that reduces ischemia-reperfusion-injury would improve the outcome of diabetic patients after a cardiovascular event. The thiazolidinedione derivatives are peroxisome proliferator-activated receptor-γ (PPARγ) ligands that are approved for the treatment of hyperglycemia in type 2 diabetes mellitus. Animal data suggest that PPARγ ligands can protect against ischemia-reperfusion-injury by improving insulin responsiveness. However, no human data on these beneficial effects are available. Recently, our group developed a human in vivo model to quantify ischemia-reperfusion-injury. In this model annexin A5 scintigraphy is used to visualize early and reversible cellular membrane changes that occur in the forearm skeletal muscle vascular bed after ischemic exercise. In the present study, we will use this approach to address the following hypothesis: Rosiglitazone reduces ischemia-reperfusion-injury in humans with insulin resistance, selected by using the criteria for the metabolic syndrome.

Study design: This is a single-center randomized, double blind, placebo-controlled crossover study with a washout period of 6 weeks.

Study population: Men and postmenopausal women, age 20-70 years with the metabolic syndrome.

Intervention: Every subject uses during 8 weeks rosiglitazone 4 mg bd and placebo bd. Week 8 and 22: assessment of ischemic-reperfusion injury with Technetium Annexin A5 Scintigraphy. Ischemic intervention: 10 minutes ischemia of the non-dominant arm with at the same time rhythmic contractions of the forearm and hand muscles.

Main study parameters/endpoints: Annexin targeting in the thenar muscle after ischemic exercise. The primary analysis is the difference in annexin targeting following 8 weeks of treatment with rosiglitazone 4 mg bd or placebo.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Ischemia-Reperfusion Injury
  • The Metabolic Syndrome
Drug: rosiglitazone
Rosiglitazone 4 mg bidaily for 8 weeks
  • Experimental: 1
    Placebo first
    Intervention: Drug: rosiglitazone
  • Experimental: 2
    Rosiglitazone first
    Intervention: Drug: rosiglitazone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
13
October 2008
July 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • At least 3 features of the metabolic syndrome (AHA/NHLBI).
  • Willing and able to provide a signed and dated written informed consent.
  • Men or postmenopausal women aged between 20 and 70 years.

Exclusion Criteria:

  • Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L, an oral 75 g glucose test will be performed to exclude diabetes mellitus.
  • Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
  • Participant in another study.
  • Angina or heart failure (NYHA I-IV).
  • Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
  • Clinically significant anemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)
  • Creatinin clearance < 40 mL/min
  • Alcohol or drug abuse.
  • Any physical inability to perform the exercise protocol.
  • Administration of any radio pharmacon for research purposes in the previous 5 years.
Both
20 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00405015
AR49653-4, EudraCT number 2006-006208-13
No
Not Provided
Radboud University
GlaxoSmithKline
Principal Investigator: Gerard A Rongen, MD, PhD Radboud University Nijmegen Medical Center, department pharmacology-Toxicology
Principal Investigator: Alexander JM Rennings, MD Radboud University Nijmegen Medical Center, department of pharmacology-Toxicology
Study Director: Paul Smits, MD, PhD Radboud University Nijmegen Medical Center, head of department of Parmacology-Toxicology
Radboud University
October 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP